Asbestosis is a form of diffuse interstitial fibrosis associated with asbestos exposure. Although asbestosis shares certain features with idiopathic pulmonary fibrosis, including increased percentages of bronchoalveolar lavage PMNs and increased uptake of 67Ga in lung parenchyma, the mechanisms(s) whereby asbestos induces pulmonary fibrosis are not known. However, observations that inhaled asbestos may be engulfed and coated by pulmonary alveolar macrophages (PAMs) with the formation of ferruginous bodies in vivo and that asbestos is cytotoxic to in vitro cultures of PAMs suggests that interactions between asbestos and PAMs might initiate the fibrotic process. Asbestos might induce fibrosis by either aleration of PAM immunoregulatory functions leading to an imbalance of the helper and suppressor forces which control local pulmonary immune responses, activation of PAMs to directly injured lung parenchuma, and/or activation of PAMs to recruit other injurious cells, such as PMNs. Our specific aims are to define the in vitro effects of amosite asbetos on: 1) Normal human PAM regulation of B-cell Ig-secretion; 2) Normal human PAM regulation of T-cell proliferative responses; 3) States of normal PAM activation, as measured by chemiluminescence, expression of Ia antigens and release PMN chemotactic factors; and 4) Normal human peripheral blood B-cell and T-cell responses. Additionally, amosite and chrysotile asbestos will be compared for their actions on PAM and peripheral blood B- and T-cell functions. The effects of coating asbestos will be assessed by comparing naked asbestos fibers with asbestos bodies (obtained from human lung digest) and with chrysotile fibers biochemically coated with Silare in similar in vitro assays. Finally, normals and patients with asbestosis will be compared for PAM regulationof B- and T-cell responses, state of PAM activation, and for differences in bronchoalveolar helper and suppressor T-cells by use of monoclonal antibodies and flow cytofluorescence. These studies should provide unique insight into how alterations in local pulmonary immunoregulation by asbestos leads to fibrosis. Furthermore, by understanding how known environmental hazards such as asbestos lead to pulmonary fibrosis, it may be possible to elucidate the pathogenetic mechanisms operative in the larger group of fibrotic disorders currently classified as idiopathic.